Biology subjects

Yasui, H.

Publications and source records attributed to Yasui, H..

3 recordsLinked to original sources

bioRxiv2020

KDM2B promotes cell viability by enhancing DNA damage response in canine hemangiosarcoma

Epigenetic regulators have been implicated in tumorigenesis of many types of cancer; however, their roles in endothelial cell cancers such as canine hemangiosarcoma (HSA) have not been studied. In this study, we found that lysine-specific demethylase 2B (Kdm2b) was highly expressed in HSA cell lines compared to normal canine endothelial cells. Silencing of Kdm2b in HSA cells resulted to increased cell death in vitro compared to the scramble control by inducing apoptosis through the inactivation of the DNA repair pathways and accumulation of DNA damage. Similarly, doxycycline-induced Kdm2b silencing in tumor xenografts resulted to decreased tumor sizes compared to the scramble control. Furthermore, Kdm2b was also highly expressed in clinical cases of HSA, and its expression levels was higher than in hemangioma, a benign counterpart of HSA. Based on these results, we hypothesized that pharmacological Kdm2b inhibition can also induce HSA cell death and can be used as an alternative treatment for HSA. We treated HSA cells with GSK-J4, a histone demethylase inhibitor, and found that GSK-J4 treatment also induced apoptosis and cell death. On top of that, GSK-J4 treatment in HSA tumor-bearing mice decreased tumor sizes without any obvious side-effects. In this study, we demonstrated that Kdm2b acts as an oncogene in HSA by enhancing DNA damage response and can be used as a biomarker to differentiate HSA from hemangioma. Moreover, we indicated that histone demethylase inhibitor GSK-J4 can be used as a therapeutic alternative to doxorubicin for HSA treatment.

cancer biology↗

bioRxiv2020

Diploid male gametes circumvent hybrid sterility between Asian and African rice species

In F1 hybrids of Oryza sativa (Asian rice) and O. glaberrima (African rice), heterozygosity leads to a complete gamete abortion because of allelic conflict at each of the 13 hybrid sterility (HS) loci. We systematically produced 19 plants from the F1 hybrids of both the rice species by the anther culture (AC) method. Five of the 19 interspecific hybrid plants were fertile and able to produce seeds. Unlike ordinal doubled haploid plants resulting from AC, these regenerated plants showed various ploidy levels (diploid to pentaploid) and different zygosities (completely homozygous, completely heterozygous, and a combination). These properties were attributable to meiotic anomalies in the interspecific hybrid F1 plants. Examination of the genetic structures of the regenerated plants suggested meiotic non-reduction took place in the interspecific hybrid F1 plants. The centromeric regions in the regenerated plants revealed that the abnormal first and/or second divisions of meiosis, namely the first division restitution (FDR) and/or second division restitution (SDR), had occurred in the interspecific hybrid. Immunohistochemical observations also verified these phenomena. FDR and SDR occurrences at meiosis might strongly lead to the formation of diploid microspores. The results demonstrated that meiotic anomalies functioned as a reproductive barrier occurred before the HS genes acted in gamete of the interspecific hybrid. Although such meiotic anomalies are detrimental to pollen development, the early rescue of microspores carrying the diploid gamete resulted in the fertile regenerated plants. The five fertile plants carrying tetraploid genomes with heterozygous alleles of the HS loci produced fertile diploid pollens, implying that the diploid gametes circumvented the allelic conflicts at the HS loci. We also proposed how diploid male gametes avoid HS with the killer-protector model.

plant biology↗

bioRxiv2020

Characterization of brown adipose tissue thermogenesis in the naked mole-rat (Heterocephalus glaber), a poikilothermic mammal

The naked mole-rat (NMR) is a poikilothermic mammal that forms eusocial colonies consisting of one breeding queen, several breeding kings, and subordinates. Despite their poikilothermic feature, NMRs possess brown adipose tissue (BAT), which in homeothermic mammals induces thermogenesis in cold environments. However, NMR-BAT thermogenic potential is controversial, and its physiological roles are unknown. Here, we show that NMR-BAT has beta-3 adrenergic receptor (ADRB3)-dependent thermogenic potential, which contributes to thermogenesis in the isolated queen in non-cold environments. NMR-BAT expressed several brown adipocyte marker genes and showed noradrenaline-dependent thermogenic activity in vitro and in vivo. Although our ADRB3 inhibition experiments revealed that NMR-BAT thermogenesis slightly delays the decrease in body temperature in a cold environment, it was insufficient to maintain the body temperatures of the NMRs. In a non-cold environment, NMRs are known to increase their body temperature by a heat-sharing behavior. Interestingly, we found that the body temperatures of NMRs isolated from the colony were also significantly higher than the ambient temperature. We also show that queens, but not subordinates, induce BAT thermogenesis in isolated, non-cold conditions. Our research provides novel insights into the role and mechanism of thermoregulation in this unique poikilothermic mammal.Competing Interest StatementThe authors have declared no competing interest.View Full Text

zoology↗